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Effects of estrogen on statin‐induced toxicity in proliferating and differentiating myoblasts
Author(s) -
Mertz Chelsea Claire,
Bielman Marie,
Ball Karen L
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1152.1
Subject(s) - dapi , apoptosis , c2c12 , in vivo , myocyte , simvastatin , viability assay , tunel assay , chemistry , andrology , microbiology and biotechnology , biology , endocrinology , medicine , biochemistry , myogenesis , genetics
Estrogen (E) regulates apoptosis in a variety of cell types with antiapoptotic effects reported in skeletal myoblasts. Interestingly, it has been suggested that in vivo females are more susceptible to myotoxicity from statin use. Our aim was to assess the role of E in simvastatin (SS) induced apoptosis in myoblasts. C2C12 cells were cultured in growth media (GM) and plated in 96‐well plates. After 72 hrs exposure to GM, GM + SS (10 μM), or GM + SS + E (1, 0.1, 0.01, 0.001, 0.0001 μM) an MTS cell viability assay was run. In a separate experiment cells were stained with DAPI to quantify apoptotic nuclei. To measure SS + E effects in differentiating myoblasts, cells were maintained in GM until confluent then exposed to the following differentiation media: DM, DM+ SS (10 μM), or DM+ SS + E (0.1, 0.01, 0.001 μM) for 72 hours. Cells were DAPI‐stained and apoptotic nuclei quantified. Data was analyzed by 1‐way ANOVA; p<0.05. As in previous studies, SS decreased the number of viable cells to 45% of control. However, E had no effect at any concentration. DAPI staining showed induction of apoptosis in the presence of SS with E neither blocking or enhancing the effect. In differentiating cells, apoptotic nuclei increased from 6.5% to over 50% with SS. Again, E had no effect. Further studies are needed to explain this lack of E effect in vitro with reported in vivo female susceptibility to statin‐induced myotoxicity. Supported by NSF STEP Grant